EphA2 And EphA3 Maintain Tumour Initiating Cells And Are Therapeutic Targets In Brain Cancer
Funder
National Health and Medical Research Council
Funding Amount
$612,860.00
Summary
High-grade glioma (HGG) is the most common adult brain cancer; current treatments have increased survival times by months only. Our studies have shown brain cancer specific expression of a family of cell surface proteins called Eph receptors. Furthermore we have shown targeting these receptors with Eph antibodies leads to a significant reduction in brain cancer tumour growth. We now propose to test targeting these receptors in combination to achieve greater responses with minimal side effects.
Antibody-based Inhibition Of ADAM10 As Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$652,788.00
Summary
Despite our advances in understanding the molecular basis of cancer, treatments for metastatic cancers are limited, emphasising an urgent need for strategies targeting several oncogenic pathways. We generated monoclonal antibodies effectively blocking the activity of ADAM10, an oncogenic cell surface protease that activates tumour growth, invasion and metastasis through multiple pathways. Here we describe the strategies that progress these antibodies as lead therapeutics for clinical testing.
EphA3 Is A Marker Of Glioma Stem/progenitor Cells And A Potential Target For Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
EphA3 is a cell surface marker which is enriched on glioma ‘propagating’ stem cells (GSCs) and furthermore has a functional role in regulating GSC differentiation and fate determination. EphA3 therefore provides a novel therapeutic target for high-grade glioma.
Inhibiting Tumour Growth By Targeting EphA3 And Disrupting Tumour Stromal And Vascular Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$645,136.00
Summary
Tumours consist of cancer cells, tumour blood vessels and connective tissue, all of which are different to normal tissues. Many of the cells making up tumour vessels and connective tissue are recruited, during initial growth and subsequent spreading of tumours, from the bone marrow. Our research will examine the presence and function of the EphA3 receptor on these cells during tumour development and assess how our anti-EphA3 antibody inhibits tumour growth by targeting stroma and vasculature.
Defining Mechanisms Of Androgen Receptor Action That Impede Breast Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$770,619.00
Summary
Androgens (A), commonly considered male hormones, are present in women and may protect them from developing aggressive breast cancer by opposing the cancer-promoting effects of estrogen (E) hormones. We propose that a disturbance in the balance between A and E action in breast cancer worsens the disease and results in a poor outcome for afflicted women. We aim to define how A and E hormones interact in breast cancer, with a view to developing new ways to treat breast cancer and predict outcome.
Understanding Intrinsic And Acquired Resistance To Anti-FGFR Therapies
Funder
National Health and Medical Research Council
Funding Amount
$797,051.00
Summary
In vitro and in vivo preclinical data suggests that inhibition of FGFR in endometrial cancer patients may be a viable therapeutic approach. Data from other cancers suggests that despite remarkable initial responses to kinase inhibitors, cancer cells eventually develop resistance. This project aims to identify and characterize the mechanisms of resistance that emerge following FGFR inhibition in order to design combination therapies that may delay and/or prevent the emergence of resistance.
An Integrated Systems Biology Approach For The Development Of New Therapeutic Strategies For The Treatment Of High Grade Glioma
Funder
National Health and Medical Research Council
Funding Amount
$696,404.00
Summary
Glioma, the most common adult brain cancer, is incurable. Recent advances now allow us to grow glioma cells directly from patients in the laboratory in a way that preserves the features of the original tumor. In this proposal we will systematically analyze such cells using state-of-the-art technologies to identify new processes important to glioma, which in turn should facilitate the identification of innovative therapeutic approaches.
Targeted Molecular Therapies And Predictive Biomarkers In A Novel Orthotopic Xenograft Model Of Oesophageal Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
Oesophageal cancer is the most rapidly increasing malignancy in Western society. This disease often presents in advanced stages with poor response to established medical and surgical therapies. Our aim is to develop a novel mouse model of oesophageal cancer, allowing us to tailor cancer-inhibiting molecular treatments to individual patients by predicting therapeutic success or resistance with the use of cellular markers identified in our animal mode.